Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York.
Department of Radiation Oncology, University of Colorado School of Medicine, Aurora, Colorado.
Int J Radiat Oncol Biol Phys. 2023 Sep 1;117(1):53-63. doi: 10.1016/j.ijrobp.2023.03.036. Epub 2023 Mar 12.
The optimal dose and fractionation of stereotactic body radiation therapy (SBRT) for locally advanced pancreatic cancer (LAPC) have not been defined. Single-fraction SBRT was associated with more gastrointestinal toxicity, so 5-fraction regimens have become more commonly employed. We aimed to determine the safety and maximally tolerated dose of 3-fraction SBRT for LAPC.
Two parallel phase 1 dose escalation trials were conducted from 2016 to 2019 at Memorial Sloan Kettering Cancer Center and University of Colorado. Patients with histologically confirmed LAPC without distant progression after at least 2 months of induction chemotherapy were eligible. Patients received 3-fraction linear accelerator-based SBRT at 3 dose levels, 27, 30, and 33 Gy, following a modified 3+3 design. Dose-limiting toxicity, defined as grade ≥3 gastrointestinal toxicity within 90 days, was scored by National Cancer Institute Common Terminology Criteria for Adverse Events, version 4. The secondary endpoints included cumulative incidence of local failure (LF) and distant metastasis (DM), as well as progression-free and overall survival PFS and OS, respectively, toxicity, and quality of life (QoL) using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (QLQ-C30) and the pancreatic cancer-specific QLQ-PAN26 questionnaire.
Twenty-four consecutive patients were enrolled (27 Gy: 9, 30 Gy: 8, 33 Gy: 7). The median (range) age was 67 (52-79) years, and 12 (50%) had a head/uncinate tumor location, with a median tumor size of 3.8 (1.1-11) cm and CA19-9 of 60 (1-4880) U/mL. All received chemotherapy for a median of 4 (1.4-10) months. There were no grade ≥3 toxicities. Two-year rates (95% confidence interval) of LF, DM, PFS, and OS were 31.7% (8.6%-54.8%), 70.2% (49.7%-90.8%), 20.8% (4.6%-37.1%), and 29.2% (11.0%-47.4%), respectively. Three- and 6-month QoL assessment showed no detriment.
For select patients with LAPC, dose escalation to 33 Gy in 3 fractions resulted in no dose-limiting toxicities, no detriments to QoL, and disease outcomes comparable with conventional RT. Further exploration of SBRT schemes to maximize tumor control while enabling efficient integration with systemic therapy is warranted.
立体定向体部放射治疗（SBRT）治疗局部晚期胰腺癌（LAPC）的最佳剂量和分割尚未确定。单次分割 SBRT 与更多的胃肠道毒性相关，因此 5 次分割方案变得更为常用。我们旨在确定 LAPC 三分割 SBRT 的安全性和最大耐受剂量。
2016 年至 2019 年，纪念斯隆凯特琳癌症中心和科罗拉多大学同时开展了两项平行的 1 期剂量递增试验。有组织学证实的 LAPC 患者，在至少 2 个月的诱导化疗后没有远处进展，符合入组条件。患者接受 3 次分割的直线加速器 SBRT，剂量水平分别为 27、30 和 33 Gy，采用改良的 3+3 设计。定义 90 天内出现≥3 级胃肠道毒性为剂量限制性毒性（DLT），采用国立癌症研究所不良事件常用术语标准，版本 4 进行评分。次要终点包括局部失败（LF）和远处转移（DM）的累积发生率，以及无进展生存期（PFS）和总生存期（OS）、毒性和生活质量（QoL），分别采用欧洲癌症研究与治疗组织生存质量问卷（QLQ-C30）和胰腺癌特异性 QLQ-PAN26 问卷进行评估。
共纳入 24 例连续患者（27 Gy：9 例，30 Gy：8 例，33 Gy：7 例）。中位（范围）年龄为 67（52-79）岁，12 例（50%）肿瘤位于头部/钩突，中位肿瘤大小为 3.8（1.1-11）cm，CA19-9 为 60（1-4880）U/mL。所有患者中位接受 4（1.4-10）个月的化疗。无≥3 级毒性。2 年 LF、DM、PFS 和 OS 的累积发生率（95%置信区间）分别为 31.7%（8.6%-54.8%）、70.2%（49.7%-90.8%）、20.8%（4.6%-37.1%）和 29.2%（11.0%-47.4%）。3 个月和 6 个月的 QoL 评估显示没有损害。
对于特定的 LAPC 患者，3 次分割至 33 Gy 未导致剂量限制性毒性，没有对 QoL 产生不利影响，且疾病结果与常规放疗相当。进一步探索 SBRT 方案以最大程度地控制肿瘤，同时使系统治疗的效率最大化是必要的。
